Eduardo Izquierdo's research notebook

My main academic website had been hosted at Sussex University for the past 6+ years. The design had not changed either, even though I had stop liking it long ago. I’m changing the design entirely, all towards minimalism.

The main reason for choosing an online service is that I won’t have to maintain html files on my computer and I won’t have to upload them to a server. It also means I can update the website from anywhere, as long as there is access to the internet. The main reason for choosing tumblr (over wordpress) is that I like the aesthetics much better.

Even though the new website looks like a traditional website, with a few static pages that hold the long-term content, because of its design, it has the opportunity to serve also as a blog. I’m not yet sure whether I will be posting things (news, what I’m working on, interesting articles I’m reading). If I do, it will be strictly academic and relevant to my research. And if so, it will be replacing this blog (I have yet to decide). At any rate, that’s another reason for the change: to unite the static with the dynamic.

Next Tuesday (31st Aug., 3:30pm in Arun-401) we will have a special seminar by one of our L&M alumni, Dr. Eduardo Izquierdo. He will give a presentation of his recent work on the topic of: Evolution and analysis of minimal neural circuits for klinotaxis in C. elegans Eduardo Izquierdo Chemotaxis during sinusoidal locomotion in nematodes captures in simplified form the general problem of how dynamical interactions between the nervous system, b … Read More

Abstract: Chemotaxis during sinusoidal locomotion in nematodes captures in simplified form the general problem of how dynamical interactions between the nervous system, body, and environment are exploited in the generation of adaptive behavior. We used an evolutionary algorithm to generate neural networks that exhibit klinotaxis, a common form of chemotaxis in which the direction of locomotion in a chemical gradient closely follows the line of steepest ascent. Sensory inputs and motor outputs of the model networks were constrained to match the inputs and outputs of the C. elegans klinotaxis network. We found that a minimalistic neural network, comprised of an ON- OFF pair of chemosensory neurons and a pair of neck muscle motor neurons, is sufficient to generate realistic klinotaxis behavior. Importantly, emergent properties of model networks reproduced two key experimental observations that they were not designed to fit, suggesting that the model may be operating according to principles similar to those of the biological network. A dynamical systems analysis of 77 evolved networks revealed a novel neural mechanism for spatial orientation behavior. This mechanism provides a testable hypothesis that is likely to accelerate the discovery and analysis of the biological circuitry for chemotaxis in C. elegans.

Imagine you are the editor of two journals, one with higher impact than the other. You receive two modeling papers, one with more predictions than validations and vice-versa. You can only accept one to each journal. Where would you send each?

What I’m asking is: How do you gauge the importance of a data-driven* model? By the number of predictions (including the proposal of novel experiments) that it makes or by the number of existing experiments that it agrees with? If both, then how would you weight each different types of contributions?

* I specify data-driven models to separate them from theory-driven models.

The Journal of Neuroscience published a series of articles commemorating the 40th anniversary of the society for neuroscience. In an attempt to follow the footsteps of mathematicians, nobel laureate Eric Kandel proposed 11 open problems for the future of understanding memory:

1. How does synaptic growth occur, and how is signaling across the synapse coordinated to induce and maintain growth?

2. What trans-synaptic signals coordinate the conversion of short- to intermediate- to long-term plasticity?

3. What can computational models contribute to understanding synaptic plasticity?

4. Will characterization of the molecular components of the presynaptic and postsynaptic cell compartments revolutionize our understanding of synaptic plasticity and growth?

5. What firing patterns do neurons actually use to initiate LTP at various synapses?

6. What is the function of neurogenesis in the hippocampus?

7. How does memory become stabilized outside the hippocampus?

8. How is memory recalled?

9. What are the role of small RNAs in synaptic plasticity and memory storage?

10. What is the molecular nature of the cognitive deficits in depression, schizophrenia, and non-Alzheimer’s age-related memory loss?

Unlike the 23 problems confronting mathematics proposed by David Hilbert, the vagueness of most of Kandel’s open questions suggest an even grander question: What is needed in the study of biological memory to allow us to propose more concrete and formal questions?

Eric R. Kandel (2009) The Biology of Memory: A Forty-Year Perspective. The Journal of Neuroscience 29(41):12748-12756.

Unlike the 23 problems confronting mathematics proposed by David Hilbert, the vagueness of most of Kandel’s open questions suggest an even grander question: What is needed in the study of biological memory to allow us to propose concrete, formal questions?

“Neuroscience has always had models, but prior to the invasion of the theorists, these were often word models. Equations force a model to be precise, complete, and self-consistent, and they allow its full implications to be worked out.”

“A skillful theoretician can formulate, explore, and often reject models at a pace that no experimental program can match. This is a major role of theory – to generate and vet ideas prior to full experimental testing. [….] Is the theorist’s job to develop, test, frequently reject, and sometimes promote new ideas. […] (to) provide valuable new ways of thinking. ”

“Identifying the minimum set of features needed to account for a particular phenomenon and describing these accurately enough to do the job is a key component of model building. […] The truly realistic model is as impossible and useless a concept as Borges’ ‘map of the empire that was of the same scale as the empire and that coincided with it point for point’”

And curiously, with regards to the ‘future': “Learning is widely considered a job for the synapse.” and “We (…) commonly tend to think of synapses as the focus of learning and memory, and neurons as the workhorses of dynamic computation. This may be radically wrong.”

Hmn.. Is he honestly not aware of the existence of the works below providing proofs of principle of how radically wrong it could be? Or is he choosing to ignore them? And if so, it would be interesting to know why exactly.

But perhaps more importantly, these suggests that the project of synaptic plasticity and leaning behavior has to reach a high impact journal where it can be read more widely and take a shape that biologists won’t so easily continue to ignore – this I am working on.

The other point that completely escapes this theoretical neuroscience review is the role that environmental feedback and the biomechanics of the body play on behavior. Not a brief mention, not even for the future! I guess this is exciting.

In order to better understand the motion and interactions of the planets (and their satellites) of our solar system, Galileo built mechanical devices to instantiate idealized models of the solar system such as the one in the figure:

Learned about this from Edward Tufte’s “Envisioning Information” and thought it would be worth sharing. This photo is from William Pearson, in Abraham Rees ed., The Cyclopaedia; or, Universal Dictionary of Arts, Sciences, and Literature, Plates, Vol. iv (London 1820).

I think this is a good example of how Galileo placed an emphasis on idealization and understanding by building in science. Not to mention early precursors to the use of computer simulations in science. Interestingly, Tufte warns that these machines may be “directing attention more toward miraculous contraptionary display than to planetary motion.” An important warning for scientists using computer simulations for modeling in general Today.

The only articles I can’t fully recommend are those by William Bechtel and by Volker Grimm and Steven F. Railsback – the message of their commentaries is unclear to me and suggests that they could possibly be a bit confused themselves about it (but I’ll re-read them a few times more just in case).

Modeler myopia is a refractive defect of the “mind’s eye of the modeler” in which biological relevance is only in focus when proximally related to empirical data; but otherwise all relevance comes out of focus.

I started by checking the area that I’m most familiar with: neural networks that can produce learning behavior. Immediately I see that the authors neglected to cite original work; citing, in one case their own version of the work (produced a decade later), and – worst yet – in a second example, adopting some ideas as their own without any reference whatsoever.

The two examples are from page 264, in a closing remarks section on neural networks.

They start off by neglecting the original work :
“.. it has been shown that .. a network with dynamic neurons and without synaptic plasticity is still capable of displaying learning-like behaviors (reference to Floreano and student paper).”

The authors follow this by describing a perspective that has been put forward by Randall Beer many times and in many different contexts, in both written form and talks. Also by Inman Harvey, but I think slightly later:
“These .. examples challenge the more or less implicit assumption that neural activations are responsible for behavior and synaptic change is responsible for learning. An alternative perspective is to consider the brain as a dynamical system characterized by several time constants associated to various processes… Such a dynamical system perspective does not require us to make a mechanistic distinction between behavior and learning of the network.”

Interestingly, this is – in my perspective – the most sensible stand, although by far still not the conventionally accepted one. So, although I think it is great to see that he considers the position to be important (even though treated only in passing during the closing remarks), I think it is not so great that he has failed to mention the people that have either: performed the original experiments or developed the ideas further.

At any rate, the lamentable thing is that while this doesn’t matter for this area, because I’m quite familiar with it and can trace back the original ideas without much effort. I’m not so sure how I feel about reading about any of the rest of the areas that I’m less familiar with, from fear that much the same will be happening throughout this book.